A Different Radiotherapy Strategy for Swallowing Difficulties in Head and Neck Cancer

Difficulty swallowing is one of the most common side effects of radiotherapy, which is frequently used for head and neck cancers. It can sometimes become severe enough for patients to need a permanent gastrostomy feeding tube. Lancet Oncology published a new UK study on July 6, 2023 that outlines a strategy to help relieve this problem.

Why Swallowing Difficulties Matter in Head and Neck Cancer

Pharyngeal (throat) cancers are common cancers affecting around 3000 patients in England each year. For most newly diagnosed patients, treatment usually involves radiotherapy or chemoradiotherapy. These treatments cure cancer in many patients but may impair quality of life. The most common long-term side effects of radiotherapy are dry mouth, swallowing difficulties (dysphagia) and soft-tissue fibrosis (tissue hardening).

Swallowing dysfunction after radiotherapy has several causes, but largely results from radiation delivered to the pharyngeal muscles responsible for initiating and completing swallowing. The pharyngeal wall contains an inner longitudinal muscle layer and an outer circular layer comprising three pharyngeal constrictor muscles. Structures at risk in the swallowing mechanism include the superior, middle and inferior constrictors, the glottis and supraglottic larynx, and the anterior oral cavity.

What Evidence Existed Before This Study?

Before beginning the study, the team reported searching PubMed, a database of medical and scientific literature, using:

• "head and neck cancer" AND
• ("radiotherapy" OR "radiation" OR "IMRT") AND
• ("dysphagia" OR "DARS" OR "MDADI" OR "swallowing outcomes") AND
• "randomized trial" as search terms.

They sought studies published in any language between August 1, 2000 and August 1, 2022. No randomized studies, in which patients were assigned to trial arms at random, were identified on this topic.

The literature showed poor long-term swallowing outcomes in most head and neck cancer patients after radiotherapy. Observational data suggested a relationship between the radiation dose to pharyngeal muscles and subsequent swallowing function, with lower doses linked to better outcomes. Phase 2 data from small, single-center, nonrandomized trials suggested improved swallowing when IMRT reduced the dose to specific parts of these muscles to 50 Gy or less.

What Does This Study Add to Practice?

To our knowledge, this is the first trial in head and neck cancer to compare "dysphagia-optimized IMRT" (DO-IMRT: Dysphagia Optimized-IMRT) with "standard IMRT" in phase 3.

DO-IMRT reduces the radiation dose to the pharyngeal constrictor muscles. This study shows better swallowing function after 12 months in patients receiving DO-IMRT than in those receiving standard IMRT.

Study Details

The team, led by Dr. Christopher Nutting, wanted to assess whether a new radiotherapy approach could reduce the swallowing problems patients commonly experience.

The trial randomized 112 patients with T1-4, N0-3, M0 oropharyngeal cancer (the region between the mouth and pharynx; 90 percent) or hypopharyngeal cancer (10 percent) to standard IMRT or DO-IMRT. They were treated between 2016 and 2018 at 22 radiotherapy centers in Ireland and England.

Most patients also received chemotherapy. Standard IMRT delivered 65 Gy to the primary tumor and involved lymph nodes and 54 Gy to other pharyngeal and nodal regions. In the DO-IMRT group, radiation to pharyngeal constrictor muscles outside the tumor target volume was limited to 50 Gy.

Results

After one year, the 56 patients receiving DO-IMRT (Dose Optimized Intensity Modulated Radiation Therapy) scored an average of 7.2 points higher on the MD Anderson Dysphagia Inventory (MDADI) than the 56 receiving standard IMRT (Intensity Modulated Radiation Therapy). The difference was statistically significant (p= 0.037). MDADI is a validated scale used to monitor radiation-related swallowing difficulties (dysphagia). Higher scores indicate better swallowing function.

Patients receiving DO-IMRT were also more likely to maintain their normal diet and eat in public. Speech and language therapists unaware of treatment allocation reported better outcomes in the DO-IMRT group.

Over approximately three years of follow-up, cancer outcomes were similar in both groups. Each had two local recurrences; distant metastatic recurrences occurred in three DO-IMRT patients and two standard IMRT patients.

The most common grade 3-4 late adverse events included hearing impairment (16% with DO-IMRT versus 13% with standard IMRT), dry mouth (5% versus 15%) and swallowing difficulties (dysphagia; 5% versus 15%).

Commentary

These findings suggest that reducing the dose to the pharyngeal constrictor muscle provides a "meaningful benefit" to patients by improving swallowing function.

However, Dr. Sandra Nuyts, a radiation oncologist at Leuven Cancer Institute, noted that the study failed to achieve the prespecified 10-point difference for clinical significance.

Other patient- and clinician-reported secondary outcomes appear to favor DO-IMRT. Together with positive findings from smaller, nonrandomized studies, there is strong evidence that this technology can reduce swallowing difficulties after head and neck radiotherapy without increasing the risk of cancer recurrence.

The researchers and Nuyts said further refinements are needed, particularly to identify which specific portions of the constrictor muscles should be spared to optimize outcomes.

For now, researchers noted a limit to "how many organs can be spared with the current DO-IMRT technique," because "using narrower margins around the tumor" risks undertreating the cancer.